The Italian defender is set for surgery on a hamstring problem next week that will rule him out of action for the remainder of the campaign.
Pascali was forced out of last weekend's 3-0 win over Hearts
before discovering the severity of the injury.
Boss Kenny Shiels said: "He's out for the season and it's a big blow for us.
"We really feel for him because he is such a good person around the players and he's a good captain.
"We are going to miss him off the pitch and on the pitch.
"It's really difficult to take in, the way we have been hit. We have taken a big hit since January.
"The boys have stepped up and we need them to step up again. It's a big loss."
Pascali endured a similar setback this time last year when he suffered a broken leg - a month before Kilmarnock lifted the Scottish Communities League Cup.
Shiels added: "He had the injury going into last season's final and we've got a cup quarter-final this time so it's going to be difficult for him but he's a strong boy."
Shiels has other selection issues ahead of this weekend's visit of Aberdeen in the Scottish Premier League.
Momo Sissoko is struggling with a virus and is rated doubtful, while Jeroen Tesselaar has been told he cannot play wearing a cast after hurting his hand in training.(re-opens) Pascali was determined to remain positive despite the lengthy lay-off and urged Kilmarnock to enjoy a successful conclusion to the campaign without him.
He told STV: "You don't have to worry about me. I'm a very positive character and I've always been taught to see the bright side of life and I know there is far, far worse.
"It's annoying that in one year I've had two bad injuries but I can do nothing now. It's not in my character to say: 'Manu, that's a shame'.
"I think they will do very, very well without me but I will try to be as close to the team as possible.
"I hope we will finish in the top six and maybe with another trophy. Then I would be happy."